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Biological Chemistry

Sour Revealed

Sleuthing pegs taste-bud cells, proteins dedicated to sensing sour substances

by Ivan Amato
August 28, 2006 | A version of this story appeared in Volume 84, Issue 35

SOUR SIGNS
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Credit: Courtesy of Nicholas Ryba and Charles Zuker
A red fluorescent label that binds specifically to a newly found sour receptor distinguishes sour-sensing cells in taste buds (on a grey background of tongue tissue) from sweet-, bitter-, and umami-sensing cells, which are all marked with green fluorescent tags.
Credit: Courtesy of Nicholas Ryba and Charles Zuker
A red fluorescent label that binds specifically to a newly found sour receptor distinguishes sour-sensing cells in taste buds (on a grey background of tongue tissue) from sweet-, bitter-, and umami-sensing cells, which are all marked with green fluorescent tags.

Having shown in recent years that three of the five basic taste modalities−bitter, sweet, and the savory taste of monosodium glutamate known as umami−work via dedicated subpopulations of taste cells and receptors, Charles S. Zuker of the University of California, San Diego, and his colleagues set out in search of a dedicated framework for sour detection.

In a sleuthing exercise summoning bioinformatics, genetic studies, and behavioral tests with mice, a research team led by Zuker and Nicholas J. P. Ryba of the National Institute of Dental & Craniofacial Research, Bethesda, Md., found what they were looking for (Nature 2006, 442, 934).

First, they scanned the mouse genome for DNA sequences indicative of receptor proteins that span cell membranes. Assuming that taste receptors would be rare in the body, they screened the resulting 10,000 hits for ones expressed only rarely among body tissues, including taste buds. That left nearly 900 candidates. Of these, the researchers pegged about 30 taste-cell-related genes with a technique that uses messenger RNA from taste bud cells like selective fishing hooks that snag only DNA sequences that can bind to the taste-cell mRNA.

The researchers found that only one of these DNA sequences, corresponding to the ion-channel protein PKD2L1, is expressed in a subset of taste bud cells separate from those dedicated to sweet, bitter, or umami tastes. What's more, mice engineered to lack cells expressing PKD2L1 were completely insensitive to sour stimuli.

"Our work identifies the cells and the strategy for mediating sour taste," Zuker says. Two other research groups independently applied molecular and cell-based assays to recently identify PKD2L1 and a partner protein as candidates for the sour taste receptor (Proc. Natl. Acad. Sci. USA 2006, 103, 12569; J. Neurochem. 2006, 98, 68).

Zuker says he is confident that he or others will eventually identify cells dedicated to salty taste.

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